Study On Asymmetric Addition Of Deactived Grignard Reagent To Aldehyde

Grignard reagents are among the most important and traditional organometal reagents.Addition of Grignard reagents to double bond is one of most reliable methods for forming Carbon-Carbon bonds.Catalytic asymmetric addition of Grignard reagents to aldehydes can produce numerous chiral sec-alcohols,many of them have different biologically activities. However,there are few success report on asymmetric alkylation by Grignard reagents due to the intrinsic high reactivities of Grignard reagents to carbonyl compounds.For a very long time,many research groups focus on using more than a stoichiometric amount of a chiral auxiliaries to obtain high enantioselectivity.There were mainly two sorts of processes be reported on highly catalytic asymmetric addition of Grignard reagents to aldehydes. The former case was transferred Grignard reagent RMgX into other organometat reagents such as R₂Zn or R-Ti derivatives via complicated procedures at extremely low temperature.The later case was directly linking a chiral ligand to Mg in the form of organomagnesium amides or use chilral amine ligand catalysis the alkylation of aldehydes.We reduced the activities of Grignard reagents successfully by complexing with Ti(OiPr)₄ and bis[2-(N,N-dimethylamino)ethyl]ether(BDMAEE)in ice-water temperature.The amount of (S)-BINOL,Ti(OiPr)₄ and RMgBr have great effects on the enantioselection.Under the optimized reaction condition,moderate to good enantioselectivities in the alkylation of aldehydes were achieved,i-BuMgBr was the best one and its enantioselection was up to 98%. Under these conditions,varieties of aryl aldehydes were used to test this reaction,and their enantioselections were all over 97%and the highest two samples were over 99%.